Camptothecin is one of the most impressive anticancer molecule of the recent years because it is the first compound found to directly block the topoisomerase (Topo-I), a DNA replication enzyme, thus stopping cell division. It was originally isolated from a rare Chinese plant Camptotheca acuminata Decne (Nyssacea) by Prof. Wall and co-workers in 1966 under the natural anticancer agent screening programme, carried out by the National Cancer Institute (NCI), USA.
Because of the noteworthy activities of camptothecin towards L 1210 in mice and walker 256 tumor in rats, camptothecin has been a molecule of great interest from the time of its initial isolation, but due to low solubility and high toxicity, its therapeutic utility was restricted for a long time in various parts of the world. However, at the same time it was used in China for the treatment of liver carcinoma and tumors of head and neck. Recently scientist around the world carried out tremendous work on the chemical transformation of camptothecin into analogs having potential anticancer activities, better solubility and less toxicity. Finally, success has been achieved and two camptothecin derived drugs, Topotecan (Hycamtin) and Irinotecan (CPT-II, Camptosar) have been approved by the FDA for the treatment of ovarian, lung and colorectal cancers. 9-Nitrocamptothecin (Orathecin) another camptothecin derived drug is expected to receive FDA approval for pancreactic cancer treatment soon. Simultaneously 9-Aminocamptothecin (9-AC) has also been introduced in clinical trials because it exhibited curative ability against human colon carcinoma and strong antitumor activity against solid tumor xenographts. There are 12 other camptothecin derived drugs, which showed promising results and are in clinical trials. Camptothecin anologs have also been demonstrated to be potent antiviral, anti-HIV agents and chemosterilants. Thus, camptothecin will have broader uses and worldwide demand of camptothecin (CPT) will dramatically increase.
Presently, CPT production relies primarily on the extracts from Camptotheca acuminata Decaisne. Although trees of C. acuminata grow fast but since many parts of this tree are being used for the extraction of camptothecin, C. acuminata is becoming endangered in many parts of the world, particularly in China.
In India camptothecin is being isolated from various parts of Indian Nothapodytes foetida (formerly Mappia foetida) Miers (Icacinaceae) in about 0.01-0.15%. Nothapodytes foetida is a small tree abundant in Western Ghats of India. Literature indicates many reports on distribution, isolation, characterization and biological activities of camptothecin and its various derivatives. Presently, camptothecin is mainly isolated from the roots of Nothapodytes foetida, To isolate 1 Kg of camptothecin, more than 1000 Kg of roots are required, thus leading to uprooting or destruction of several thousands of plants.
This destruction method of camptothecin isolation from the roots of N. foetida is the biggest drawback of the existing processes. This prompted us to research into a non-destructive method of camptothecin isolation and develop an easy and economical process for isolation of this anticancer agent, thereby bringing it within the reach of the common people.
A literature survey revealed that an isolation procedure for camptothecin from stem of Mappia foetida syn Nothapodytes foetida (“Alkaloids of Mappia foetida”, Govindachari and Visvanathan, 1972, Phytochenmistry, 11, 3529-3531) has been reported. The process involved defatting of powdered stem twice with hexane followed by successive cold extraction thrice with Me2CO and MeOH Extracts were combined separately, concentrated under vacuum and left in ice chest for a week to give a greenish white solid, which on triangular crystallization results in the isolation of camptothecin in 0.11% yield.
The method described above suffers from a number of disadvantages. The biggest disadvantage of the above process is the poor yield of camptothecin (0.11%) when compared with ours (0.15%). The second disadvantage of the above method is that it uses cold percolation process where plant material is left over night in a solvent for each percolation, hence for complete extraction (twice with hexane, thrice with Me2CO and twice with MeOH) of plant material at least seven days are required. The third disadvantage of the above method is that it requires more solvent, more electricity, more manpower and more time, thus resulting in an expensive and time taking process for the isolation of camptothecin from the twigs and stem of N. foetida. 